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Itraconazole: A Quick Guide For Clinicians

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Dr Atul K Patel, MD, FIDSA
Chief Consultant and Director
Infectious Diseases Clinic
Vedanta Institute of Medical Sciences
Ahmedabad, India

Itraconazole is a first-generation azole drug that became available in the 1990s. Itraconazole and other azoles disrupt the integrity of fungal cell membranes by interfering with ergosterol synthesis, leading to fungal cell death.

Itraconazole exhibits minimal activity against the Fusarium species, and it has no activity against most Mucorales.

Spectrum of activity


Dimorphic fungi

Mycelial fungi


Most Candida spp., with higher MICs for C. glabrata and C. krusei


Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp

Aspergillus spp., including A. fumigatus, A. flavus, A. nidulans and A. terreus


Cryptococcus neoformans

Talaromyces marneffei (formerly Penicillium marneffei), Sporothrix schenckii

Entomophthorales, eg, Conidiobolus and Basidiobolus



Yeast: Mucosal candidiasis, cryptococcal infection (not as a primary agent, but it can be used as an alternative agent for chronic suppressive therapy).

Dimorphic fungi: For mild-to-moderate disease, itraconazole can be used as initial therapy. For severe diseases, amphotericin B is recommended for initial therapy, followed by itraconazole.

Mycelial fungi: As second-line treatment of invasive Aspergillus infection. Itraconazole is commonly used for chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis treatment.1

Itraconazole is used for empiric treatment of fungal infection in neutropenic patients.2

It is also used successfully in the treatment of infections caused by Entomophthorales (basidiobolomycosis, conidiobolomycosis).3

Dosage and forms

For most systemic fungal infections, itraconazole 200–400 mg per day is given, except for life-threatening infections, where 200 mg 3 times/day (ie, 600 mg) is given as a loading dose for 3 days, followed by 400 mg/day.

Itraconazole is available in 2 oral preparations, as capsules and as an oral solution. Intravenous itraconazole is currently not available. Only the capsule form is available in India.


The absorption and bioavailability of these 2 oral formulations are different. The oral bioavailability of the capsule formulation is approximately 55% and is improved with gastric acidity and food intake.4 It is generally recommended to be taken with an acidic beverage (such as cola) and food for better absorption. Antacids, including proton-pump inhibitors and H2 blockers, should be avoided as concomitant use significantly reduces absorption of itraconazole capsules.

The oral solution has a higher oral bioavailability of 80%, and its absorption is not affected by gastric acidity or food intake. This formulation has less interpatient variability, and patients achieve 30% higher serum concentrations than with the capsule.

Therapeutic drug monitoring for patients receiving itraconazole and its active hydroxyl itraconazole metabolite is required because of unpredictable absorption. Clinical studies have correlated itraconazole serum levels and therapeutic response for a variety of fungal infections.5 Itraconazole levels >0.5 μg/mL for antifungal prophylaxis and 1–2 μg/mL for treatment are associated with successful outcomes.6

Once-daily administration of itraconazole is generally adequate because of its long half-life of 25–64 hours. However, divided dosage is recommended for better absorption when used 400 mg or higher daily.

Currently, itraconazole clinical use is limited to: cutaneous fungal infections; allergic bronchopulmonary aspergillosis; histoplasmosis (after induction therapy with amphotericin B); and Entomophthorales infection


In general, itraconazole is fairly well tolerated. The most common side effects include rash, headache, gastrointestinal upset, transaminitis and, rarely, liver failure. Monitoring of liver chemistry tests during its use is recommended.

Drug-drug interactions

The triazoles have the highest potential for serious drug-drug interactions among antifungal agents. They are substrates and inhibitors of various hepatic CYP450 metabolic enzymes (CYP3A4, CYP2C9, CYP2C19).8 Remember that all triazoles (itraconazole, fluconazole, voriconazole) are inhibitors of CYP450 enzymes and impair the metabolism of co-administered drugs, resulting in increased exposure, higher levels and the risk of toxicity. As substrates of the pathway, the concentrations of the triazoles are also affected by concomitant use of medications that inhibit or induce these enzymes. Be careful while prescribing itraconazole to patients receiving the following classes of medicines: anti-tuberculosis, anti-HIV, anticoagulants, sedative-antidepressants, anti-arrhythmics, antipsychotics, immunosuppressants, anti-epileptics, statins, and oral hypoglycemic agents, among others. Always check possible drug interactions using available guides, such as in mobile apps.


  1. Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med 2000;342:756-762.
  2. Nucci M, Biasoli I, Akiti T, et al. A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Clin Infect Dis 2000;30:300-305.
  3. El-Shabrawi MH, Kamal NM. Gastrointestinal basidiobolomycosis in children: an overlooked emerging infection? J Med Microbiol 2011;60:871-880.
  4. Lange D, Pavao JH, Wu J, Klausner M. Effect of a cola beverage on the bioavailability of itraconazole in the presence of H2 blockers. J Clin Pharmacol 1997;37:535-540.
  5. Denning DW, Tucker RM, Hanson LH, Stevens DA. Treatment of invasive aspergillosis with itraconazole. Am J Med 1989;86(6 Pt 2):791-800.
  6. Denning DW, Tucker RM, Hanson LH, et al. Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern Med 1989;149:2301-2308.
  7. Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989;32 Suppl 1:67-87.
  8. Brüggemann RJ, Alffenaar JW, Blijlevens NM, et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 2009;48:1441-1458.

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